ABSTRACT:
P-glycoprotein (P-gp) a 170 kDa membrane-bound protein, an energy-dependent efflux transporter driven by ATP hydrolysis is an ATP binding cassette transporter located in the plasma membrane of mammalian cells actively expels a number of amphiphilic molecules that enter the cell by passive diffusion. It is present in several tissues and is thought to be involved in the protection of the whole organism against toxic xenobiotics. The overproduction of P-glycoprotein in some cancer cells is responsible for the Multidrug resistance (MDR) phenotype, reducing the effectiveness of various cytotoxic drugs used in anticancer chemotherapy. It is also found to play a role in affecting the pharmacokinetics of drugs used in CNS diseases. Therefore, understanding P-glycoprotein functioning is of importance for controlling the bioavailability of many drugs of pharmaceutical interest and for improving drug chemotherapy. The modulation of drug transporters through inhibition or induction by various drugs or herbs can lead to significant drug-drug or drug-herb interactions by affecting various pharmacokinetic parameters of the drug. P-gp has therefore attracted considerable attention as a target in the field of drug development, because for a large number of active compounds, interaction with P-glycoprotein might compromise their future development into a drug.